Phase I Study of Vidaza and Velcade (Bortezomib) in Acute Myeloid Leukemia

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS)

- High risk (by IPSS scoring)

- Relapsed or refractory disease

- Secondary AML or therapy related disease (t-AML) allowed

- No active central nervous system disease or granulocytic sarcoma as sole site of
disease

- No advanced malignant solid tumors

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Life expectancy > 6 months for patients with a co-morbid medical illness

- Total bilirubin < 2.0mg/dL

- AST/ALT < 2.5 times upper limit of normal (ULN)

- Creatinine < 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to and during study treatment

- Ability to understand and willingness to sign the written informed consent document

- Active infection is allowed provided it is under control

Exclusion criteria:

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to azacytidine or bortezomib that are not easily managed

- Hypersensitivity to bortezomib, boron, or mannitol

- Uncontrolled intercurrent illness including, but not limited to:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Serious cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study

- Myocardial infarction within 6 months prior to enrollment

- New York Heart Association (NYHA) Class III or IV congestive heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmia

- Electrocardiographic evidence of acute ischemia

- Active conduction system abnormalities

- ECG abnormality that is medically relevant

- Psychiatric conditions that prevent compliance with protocol or consent.

- Pre-existing neuropathy grade 2 or higher or other serious neurologic toxicity that
would significantly increase risk of complications from bevacizumab therapy

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study

- Diagnosis or treatment for another malignancy within 3 years of enrollment, with the
exception of any of the following:

- Complete resected basal cell carcinoma

- Squamous cell carcinoma of the skin

- Any in situ malignancy

- Low-risk prostate cancer after curative therapy

PRIOR CONCURRENT THERAPY:

- Prior decitabine or azacytidine for MDS or AML is allowed

- Prior bortezomib allowed

- More than 2 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C)

- More than 14 days since prior and no concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients